+

WO2008009275A1 - Procédé pour préparer des composés d'aminocarbonyle chiraux - Google Patents

Procédé pour préparer des composés d'aminocarbonyle chiraux Download PDF

Info

Publication number
WO2008009275A1
WO2008009275A1 PCT/DE2007/001281 DE2007001281W WO2008009275A1 WO 2008009275 A1 WO2008009275 A1 WO 2008009275A1 DE 2007001281 W DE2007001281 W DE 2007001281W WO 2008009275 A1 WO2008009275 A1 WO 2008009275A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
substituted
aryl
general formula
alkenyl
Prior art date
Application number
PCT/DE2007/001281
Other languages
German (de)
English (en)
Inventor
Benjamin List
Michael Stadler
Jung Woon Yang
Original Assignee
Studiengesellschaft Kohle Mbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Studiengesellschaft Kohle Mbh filed Critical Studiengesellschaft Kohle Mbh
Priority to EP07785650A priority Critical patent/EP2041066A1/fr
Priority to US12/373,955 priority patent/US20090281346A1/en
Priority to CA002658537A priority patent/CA2658537A1/fr
Priority to JP2009519789A priority patent/JP2009543815A/ja
Publication of WO2008009275A1 publication Critical patent/WO2008009275A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups

Definitions

  • the present invention relates to a process for the preparation of aminocarbonyl compounds from aldehydes and imines in the presence of a catalyst.
  • the corresponding imines are already known in literature or can be prepared analogously to known processes.
  • the usual synthesis involves two simple steps (Scheme 2).
  • an aldehyde is first treated with an NH 2 carbamate and the sodium salt of an arylsulfinic acid.
  • the corresponding alkyloxycarbonyl- ⁇ - (arylsulfonyl) amine is formed, which is reacted with base in a second step to the desired imine.
  • the present invention accordingly provides a process for the preparation of aminocarbonyl compounds of general formula I.
  • R 1 and R 2 may be the same or different and represent hydrogen, alkyl, alkenyl, alkynyl or aryl,
  • X is hydrogen, alkyl, alkenyl, alkynyl or aryl or is OR 3 , where R 3 is hydrogen,
  • R 2 and X have the abovementioned meaning, be implemented.
  • the reaction components are reacted in the presence of a catalyst.
  • Any catalyst can be used which aids in the reaction between the aldehyde and the imine. If chiral aminocarbonyls are to be prepared as reaction products, preference is given to using asymmetric, in particular asymmetric, organic catalysts. Particularly suitable catalysts have been found which contain one or more heteroatoms, for. Nitrogen, oxygen, sulfur or phosphorus, with nitrogen being a preferred heteroatom. Oxygen- or sulfur-containing catalysts can be, for example, alcohol and thiols, while phosphorus-containing catalysts generally dart lead phosphines. Catalysts having one or more nitrogen atoms in the molecule may be primary or secondary amines or nitrogen-containing polymers. Preferred amines have a structure with the general formula IV
  • R 5 and R 6 may be the same or different and are selected from hydrogen, hydrocarbons, especially alkyl, alkenyl, alkynyl, aryl or alkylaryl, each of which may have suitable substituents or one or more heteroatoms in the radical, or R 5 and R 6 together form a ring structure which, in addition to the N atom in the formula IV, may optionally contain a further heteroatom. If R 5 and R 6 are connected together they can, for. B.
  • R 5 and R 6 may form unsubstituted or substituted cyclopentyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, pyrrolyl, pyridinyl, pyrimidinyl, imidazolyl or the like.
  • Preferred compounds are those in which R 5 and R 6 are independently selected from methyl, ethyl, propyl, butyl, cyclopentyl, cyclohexyl. Cyclooctyl, phenyl, naphthyl, benzyl and trimethylsilyl or the like, so that a 3- to 15-membered, optionally substituted cyclic radical having the general formula V is formed
  • n 0 or 1 and X is a radical of up to 50 atoms selected from the group of substituted or unsubstituted alkylenes which may also contain heteroatoms, and each of X 1 and X 2 is independently an unsubstituted or substituted methylene group.
  • Examples of the secondary amines of formula V are compounds of general formula VI
  • R 7 , R 8 , R 9 and R 10 may be the same or different and are independently selected from hydrogen, OH, SH, carboxyl, amino, mono-C r C 24 -alkylamino, di-CrC 2 4 -alkylamino, mono- C 5 -C 24 arylamino, di-C 5 -C 24 arylamino, di-N-substituted C r C 24 - alkyl-C 5 -C 24 arylamino, C 2 -C 24 alkylamido, C 6 -C 24 -arylamido, imino, C 2 -C 24 alkylimino, C 6 - C 24 -Arylimino, nitro, nitroso, C 1 -C 24 -alkoxy, C 5 -C 24 aryloxy, C 6 -C 24 aralkyloxy, C 2 C 24 - Alkylcarbonyl, C 6 -C 24 -arylcarbonyl, C
  • X can z.
  • a group - (CR 11 R 12 ) - (X 3 ) q - (CR 13 R 14 ) t so that the amine is a compound of general formula VII
  • X 3 is O, S, NH, NR 15 or CR 16 R 17 , q is 0 or 1, t is 0 or 1 and R 11 , R 12 , R 13 , R 14 , R 16 and R 17 are independently selected from hydrogen, OH, SH 1 carboxyl, amino, mono-dC ⁇ alkylamino, di-C r C 24 alkylamino, mono ⁇ C 5 -C 24 arylamino, di-C 5 -C 24 - arylamino, di- N-substituted C r C 24 alkyl-C 5 -C 24 arylamino, C 2 -C 24 alkylamido, C 6 -C 24 - arylamido, imino, C 2 -C 24 alkylimino, C 6 -C 24 - arylimino, nitro, nitroso, C r C 24 alkoxy, C 5 -C 24 - aryloxy, C 6 -C 24
  • catalysts of the formula VI in which q 0, t 1 and at least one of the radicals R 7 to R 10 is an acidic substituent, such as a carboxyl group, in such an embodiment the compound mt of the formula VII is proline or substituted proline ,
  • a suitable catalyst is L-proline itself, a compound known from the literature which corresponds to the compound of formula VII when R 7 to R 9 and R 11 to R 14 are hydrogen and R 10 is ⁇ -carboxyl.
  • Another preferred group of catalysts are compounds in which q is 1, X 3 is NR 15 , t is 0, R 7 and R 9 are hydrogen and R 8 is CR 18 R 19 R 20 , so that the secondary amine is a Represents compound with the general formula VIIIA or VIIIB
  • R 10 has the meaning as defined above and preferably represents a group - (L) m -CR 19 R 20 R 23 , in which m is 0 or 1, L is C r C 6 -alkylene and R 21 , R 22 and R 24 is hydrocarbon of 1 to 12 carbon atoms.
  • the substituents are preferably R 8 are those in which m and R 21, R 22 and R 23 is C 0 r 2 are Ci alkyl.
  • R 21 , R 22 and R 23 are particularly preferably C 1 -C 6 -alkyl, in particular methyl, so that R 8 is a t-butyl group.
  • R 15 is selected from substituted or unsubstituted hydrocarbons having 1 to 12 carbon atoms, e.g. Alkyl, alkenyl, alkynyl, aryl, alkaryl, aralkyl, etc., which may contain one or more heteroatoms.
  • R 15 is hydrocarbyls of 1 to 12 carbon atoms, such as C r C 12 alkyl, with C r C 6 alkyl, such as methyl, ethyl, propyl, butyl, pentyl or hexyl, is preferred.
  • R 18 and R 19 are independently selected from Wassestoff, halogen, hydroxy, substituted or unsubstituted hydrocarbons having from 1 to 12 carbon atoms, which may contain one or more heteroatoms.
  • R 18 and R 19 are hydrogen or hydrocarbyl of 1 to 12 carbon atoms, with R 18 and R 19 being particularly preferred.
  • R 20 may be a cycle which may have 1 to 4 substituents and 0 to 3 heteroatoms selected from N, O and S.
  • R 20 is a monocyclic aryl or heteroaryl having up to 4 substituents selected from halogen, hydroxy, and hydrocarbon of 1 to 12 carbon atoms.
  • Particularly preferably R 20 is a phenyl group having 1 or 2 substituents such as halogen, hydroxy or C r C may have 6 alkyl, wherein R 20 is most preferably an unsubstituted phenyl group.
  • any of the compounds described above may also be used in the form of the acid addition salts, which addition salt may be used per se or may form in the course of the reaction.
  • the catalyst is usually used in an amount of 0.1 to 200 mol%, preferably from 1 to 30 mol%, based on the starting compounds
  • the imines of the general formula III can be used according to the invention directly or in the form of their molding stages, so that the imine forms in situ during the reaction.
  • alkyl as used herein means a linear, branched or cyclic hydrocarbon radical usually having from 1 to 30, preferably from 1 to 24 carbon atoms and more preferably from 1 to 6 carbon atoms, such as methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl , t-butyl, octyl, decyl, etc., but also cycloalkyl groups such as cyclopentyl, cyclohexyl, etc.
  • the hydrocarbon radicals have 1 to 18, in particular 1 to 12 carbon atoms.
  • Alkenyl in the context of the present invention means an unsaturated, linear, branched or cyclic hydrocarbon radical having one or more double bonds, which usually has between 2 and 30, preferably 2 to 24 and in particular 2 to 6 carbon atoms, such as ethenyl, n-propenyl, Isopropenyl, n-butenyl, isobutenyl, pentenyl, hexenyl, octenyl, decenyl, etc., but also cycloalkenyl groups such as cyclopentenyl, cyclohexenyl, etc.
  • Alkynyl in the context of the present invention means an unsaturated, linear, branched or cyclic hydrocarbon radical having one or more triple bonds, which usually has between 2 and 30, preferably 2 to 24 and in particular 2 to 6 carbon atoms, such as ethynyl, n-propynyl, Isopropynyl, n-butynyl, isobutinyl, pentynyl, hexynyl, octynyl, decynyl, etc., but also cycloalkynyl groups such as cyclopentynyl, cyclohexynyl, etc.
  • aromatic ring systems having 5 to 30 carbon atoms and optionally heteroatoms such as N, O, S, P, Si, used in the ring, wherein the rings single or multiple ring systems, for.
  • Ring systems or via simple bonds or multiple bonds bonded together rings can be.
  • aromatic rings are phenyl, naphthyl,
  • Substituted aryl groups have one or more substituents.
  • heteroalkyl groups are alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylated aminoalkyl and the like.
  • heteroaryl substituents are pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, Pyrimidinyl, imidazolyl, 1, 2,4-triazolyl, tetrazolyl, and the like.
  • heteroatom-containing alicyclic groups pyrrolidino, morpholino, piperazino, piperidino, etc. may be mentioned.
  • substituents which may have the abovementioned groups are OH, F, Cl, Br, J 1 CN, NO 2 , NO, SO 2 , SO 3 ' , amino, -COOH, -COO (C r C 6 alkyl ), mono- and di- (C r C 24 alkyl) -substituted amino, mono- and di- (C 5 -C 20 -aryl) -substituted amino, imino into account, which can in turn be substituted, eg C r C 6 alkyl, aryl, and phenyl.
  • the cyclic radicals may also have C r C 6 alkyl groups as substituents.
  • the process according to the invention is preferably carried out in solution.
  • at least one of the starting substances or the catalyst is dissolved in a suitable solvent, the other components are added as pure substances or in solution.
  • the solvent any organic solvents can be used which are inert to the reaction components and do not interfere in the reaction.
  • solvents examples include pentane, hexane, heptane, octane, petroleum ether, toluene, xylene, ethyl acetate, tetrahydrofuran, diethyl ether, methyl-fer-butyl ether, 1,4-dioxane, methylene chloride, chloroform, carbon tetrachloride, dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidinone , Acetonitrile, methanol, ethanol, dioxane, sulfolane, 1, 2-dichloroethane, poly (ethylene glycol) having a molecular weight between 200 and 1450, preferably between 200 and 600, ionic liquids, water and any mixtures of the foregoing, with organic solvents being preferred ,
  • the inventive method can be carried out in wide temperature ranges, usually the reaction temperature is between - 2O 0 C and 5O 0 C.
  • the reaction time is between 1 hour and 24 hours.
  • the resulting reaction product can usually be isolated from the reaction mixture and purified. In one possible embodiment, the reaction mixture is poured into water and then extracted with an organic solvent.
  • the product was purified by column chromatography on silica gel using ethyl acetate / hexane (initially 10/90, then 20/80, vol / vol) as eluent.
  • the product is obtained in 52% yield.
  • the enantiomeric ratio of the product was determined to be> 99: 1 by gas chromatography.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Furan Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un procédé pour préparer des composés d'aminocarbonyle de formule générale (I) dans laquelle R1 et R2 peuvent être identiques ou différents et représentent hydrogène, alkyle, alcényle, alcinyle ou aryle, X est hydrogène, alkyle, alcényle, alcinyle ou aryle ou représente OR3 où R3 est hydrogène, alkyle, alcényle, alcinyle ou aryle. Selon le procédé de l'invention, un aldéhyde de formule générale (II) R1CO dans laquelle R1 a les correspondances mentionnées ci-dessus, est converti en la présence d'un catalyseur avec une imine de formule générale (III) dans laquelle R2 et X ont les correspondances indiquées ci-dessus. Les réactions de Mannich catalysées avec des aldéhydes permettent d'obtenir des aminocarbonyles. Si on convertit par exemple des aldéhydes α-ramifiés avec des imines N-Boc préformées en la présence de(S)-proline en tant que catalyseur, on obtient les aminoaldéhydes ß souhaités avec d'excellents rendements, et d'excellentes disastéréosélectivités et énantiosélectivités.
PCT/DE2007/001281 2006-07-19 2007-07-17 Procédé pour préparer des composés d'aminocarbonyle chiraux WO2008009275A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP07785650A EP2041066A1 (fr) 2006-07-19 2007-07-17 Procédé pour préparer des composés d'aminocarbonyle chiraux
US12/373,955 US20090281346A1 (en) 2006-07-19 2007-07-17 Method for the production of chiral aminocarbonyl compounds
CA002658537A CA2658537A1 (fr) 2006-07-19 2007-07-17 Procede pour preparer des composes d'aminocarbonyle chiraux
JP2009519789A JP2009543815A (ja) 2006-07-19 2007-07-17 キラルなアミノカルボニル化合物の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006033362A DE102006033362A1 (de) 2006-07-19 2006-07-19 Verfahren zur Herstellung von chiralen Aminocarbonylverbindungen
DE102006033362.4 2006-07-19

Publications (1)

Publication Number Publication Date
WO2008009275A1 true WO2008009275A1 (fr) 2008-01-24

Family

ID=38728750

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2007/001281 WO2008009275A1 (fr) 2006-07-19 2007-07-17 Procédé pour préparer des composés d'aminocarbonyle chiraux

Country Status (6)

Country Link
US (1) US20090281346A1 (fr)
EP (1) EP2041066A1 (fr)
JP (1) JP2009543815A (fr)
CA (1) CA2658537A1 (fr)
DE (1) DE102006033362A1 (fr)
WO (1) WO2008009275A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012000608A2 (fr) 2010-06-30 2012-01-05 Gluesenkamp Karl-Heinz Nouveaux dérivés bêta-aminoaldéhyde, procédé de préparation de ces dérivés et leur utilisation en chimie comme intermédiaires réactifs
WO2015193921A1 (fr) * 2014-06-20 2015-12-23 Council Of Scientific And Industrial Research Synthèse asymétrique organocatalytique d'antidépresseurs

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5099932B2 (ja) * 2009-03-12 2012-12-19 独立行政法人科学技術振興機構 フルオレノンイミンを用いた炭素−炭素結合生成反応
US8962889B2 (en) * 2010-10-20 2015-02-24 Sumitomo Chemical Company, Limited Process for producing optically active β-amino aldehyde compound
CN110845369B (zh) * 2019-11-28 2022-03-18 浙江工业大学 一种达泊西汀及其中间体的合成方法
CN110845288B (zh) * 2019-11-28 2022-07-19 浙江工业大学 一种手性β-氨基醛类化合物的不对称合成方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7968734B2 (en) * 2004-07-01 2011-06-28 Stc.Unm Organocatalysts and methods of use in chemical synthesis

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
B. LIST ET.AL.: "The proline-catalyzed direct asymmetric three-component Mannich reaction: Scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohols", JACS, vol. 124, no. 5, 2002, pages 827 - 833, XP002460697 *
B. LIST: "The direct catalytic asymmetric three-component Mannich reaction", JACS, vol. 122, 2000, pages 9336 - 9337, XP002460698 *
FRANKLIN A. DAVIES ET.AL.: "Synthesis and application of nonracemic beta-amino aldehydes to the asymmetric synthesis of piperidines: (+)-Dihydropinidine", TETRAHEDRON LETTERS, vol. 39, 1998, pages 5951 - 5954, XP002460696 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012000608A2 (fr) 2010-06-30 2012-01-05 Gluesenkamp Karl-Heinz Nouveaux dérivés bêta-aminoaldéhyde, procédé de préparation de ces dérivés et leur utilisation en chimie comme intermédiaires réactifs
DE102010025663A1 (de) 2010-06-30 2012-01-05 Karl-Heinz Glüsenkamp Neue beta-Aminoaldehyd-Derivate, Verfahren zu ihrer Herstellung und ihre chemische Verwendung als reaktive Intermediate
WO2015193921A1 (fr) * 2014-06-20 2015-12-23 Council Of Scientific And Industrial Research Synthèse asymétrique organocatalytique d'antidépresseurs
US10266481B2 (en) 2014-06-20 2019-04-23 Council Of Scientific & Industrial Research Organocatalytic asymmetric synthesis of antidepressants

Also Published As

Publication number Publication date
CA2658537A1 (fr) 2008-01-24
EP2041066A1 (fr) 2009-04-01
US20090281346A1 (en) 2009-11-12
DE102006033362A1 (de) 2008-01-24
JP2009543815A (ja) 2009-12-10

Similar Documents

Publication Publication Date Title
DE69824958T2 (de) Enantioselektive additions-reaktion mit hilfe eines organozink reagenzes
WO2008009275A1 (fr) Procédé pour préparer des composés d'aminocarbonyle chiraux
DE3322530A1 (de) Verfahren zur herstellung von mono-, bi- und tricyclischen aminosaeuren
DE69532849T2 (de) Verfahren zum Epoxidieren prochiraler Olefine
DE60204334T2 (de) Verfahren zur Herstellung von Repaglinid
EP1636199A2 (fr) Procede de production de derives d'acide phenylacetique
DE60129211T2 (de) Imidazolidinonen-saureadditionssalze als reaktionskatalysatoren
US20100113786A1 (en) Phosphoramide compound, method for producing the same, ligand, complex, catalyst and method for producing optically active alcohol
EP1067129B1 (fr) La racemisation de la R,S-dioxo-benzylpyrrolopipéridine
EP0570764A2 (fr) Hydrogénation asymétrique
DE69603419T3 (de) Verfahren zur Herstellung von optisch aktiven Amiden
DE69520947T2 (de) Diarinopropanole abgeleitet von aminosäuren
DE60031299T2 (de) Verfahren zur industriellen Herstellung von (Aminomethyl)trifluormethlcarbinol-Derivaten
EP0266308A1 (fr) Dérivés de l'indolo-pyrazino-benzodiazépine
DE2659851A1 (de) Monomethylolimidazolverbindungen und verfahren zu deren herstellung
DE69825988T2 (de) Verfahren zur entfernung von schwermetallen aus organischen verbindungen
DE69333240T2 (de) Verfahren zur herstellung von enantiomerreinen fluorierten epoxychromanen
EP1819647A1 (fr) Procede d'hydrogenation de composes carbonyle $g(a),$g(b)-insatures
EP3577105B1 (fr) Préparaton d'hydroxylamines aromatiques n-substituées
EP1218349A2 (fr) Procede pour dissocier de maniere selective des anhydrides d'acides carboxyliques cycliques
DE68917994T2 (de) Verfahren zur Herstellung von Pyrrolizinderivaten.
DE3027325A1 (de) Neues papaverincarbanion und verfahren zu seiner herstellung
DE68903133T2 (de) Pyrrolizinderivat und seine herstellung.
DE958925C (de) Verfahren zur Isolierung und Reindarstellung von Methyl-bis-(ª‰-chloraethyl)-aminoxyd-hydrochlorid
DE60213604T2 (de) Verfahren zur herstellung von 4-amino-4-phenylpiperidinen

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07785650

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2007785650

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12373955

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2658537

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2009519789

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: RU

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载